VERBRUGGE, Frederik; Dupont, Matthias; Rivero-Ayerza, Maximo; De Vusser, Philippe; Van Herendael, Hugo; Vercammen, Jan; Jacobs, Linda; Verhaert, David; VANDERVOORT, Pieter; Tang, W. H. Wilson; MULLENS, Wilfried
Background: The influence of comorbid conditions on ventricular remodeling, functional status, and clinical outcome after cardiac resynchronization therapy (CRT) is insufficiently elucidated. Methods and Results: The influence of different comorbid conditions on left ventricular remodeling, improvement in New York Heart Association (NYHA) functional class, hospitalizations for heart failure, and all-cause mortality after CRT implantation was analyzed in 172 consecutive patients (mean age 71 +/- 9 y), implanted from October 2008 to April 2011 in a single tertiary care hospital. During mean follow-up of 18 +/- 9 months, 21 patients died and 57 were admitted for heart failure. Left ventricular remodeling...
Stappers, Mark H. T.; Janssen, Nico A. F.; Oosting, Marije; Plantinga, Theo S.; Arvis, Pierre; Mouton, Johan W.; Joosten, Leo A. B.; Netea, Mihai G.; GYSSENS, Inge
Bacteroides fragilis, an intestinal flora commensal microorganism, is frequently isolated from abscesses and soft tissue infections. This study aimed to identify pattern recognition receptors (PRRs) involved in B. fragilis recognition and to characterize the induced cytokine profile. Human PBMCs were stimulated with heat-killed B. fragilis and cytokine levels were determined by ELISA. Roles of individual PRRs were assessed using specific blockers of receptor signaling pathways and PBMCs carrying single nucleotide polymorphisms of PRR genes. Cell lines expressing human TLR2 or TLR4 were employed to assess TLR-specificity of B. fragilis. TLR1, TLR2 and NOD2 were the main PRRs responsible for recognition...
Knevel, Rachel; Klein, Kerstin; Somers, Klaartje; Ospelt, Caroline; Houwing-Duistermaat, Jeanine J.; van Nies, Jessica; de Rooy, Diederik P. C.; de Bock, Laura; Schonkeren, Joris; Stoeken-Rijsbergen, Gerrie; Kiridly, Jenna; Rodriguez-Rodriguez, Luis; Helmer, Quinta; Sinissen, Piet; Huizinga, Tom W. J.; Toes, Rene E. M.; Gay, Steffen; Gregersen, Peter K.; Somers, Veerle; van der Helm-van Mil, Annette H. M.
Background/Purpose: Recent genome-wide association studies (GWAs) have identified > 30 SNPs predisposing to Rheumatoid Arthritis(RA). These variants are helpful in unraveling the pathogenesis of RA. However, most therapeutic strategies target pathways of disease progression. Genetic factors account for a considerable proportion of variance in joint damage, but thus far only a few replicated severity factors are known and no GWAS has been performed. We aimed to increase the understanding of the processes underlying the inter-individual differences in joint damage in anti-citrullinated peptide anti-bodies (ACPA)-positive RA by performing a 3-staged GWAS on joint damage progression using high-quality radiology data, followed by...
GRIETEN, Lars; VERBRUGGE, Frederik; STORMS, Valerie; Verhaert, D.; Rivero-Ayerza, M.; De Vusser, P.; Van Herendael, H.; Vercammen, J.; Jacobs, L.; Rondelez, K.; MULLENS, Wilfried; VANDERVOORT, Pieter
Our aim was to test if intra-thoracic impedance (ITI) measurements would improve short-term clinical outcome (i.e. all-cause mortality and heart failure hospitalizations) in patients with cardiac resynchronization therapy (CRT) who were followed in a telemonitoring program with structural biofeedback. Methods: CRT patients (n=200; age= 70 +/-14y) were included in a telemonitoring program at Ziekenhuis Oost-Limburg Genk, which comprised daily transmissions through a wireless system installed at their homes. All patients were followed for potential lead/device problems, episodes of anti-tachycardia pacing, device shocks, occurrence of arrhytmias, a decline in biventricular pacing percentage and/or a sudden drop in physical activity. Patients with...
ROUWETTE, Myrthe; SOMERS, Klaartje; GOVARTS, Cindy; De Deyn, Peter P.; Hupperts, Raymond; VAN WIJMEERSCH, Bart; De Jong, Brigit A.; Verbeek, Marcel M.; Van Pesch, Vincent; Sindic, Christian; Villar, Luisa M.; Alvarez-Cermeno, Jose C.; STINISSEN, Piet; SOMERS, Veerle
Limited information is available on the identity of antigens targeted by antibodies present in cerebrospinal fluid (CSF) of patients with clinically isolated syndrome (CIS). The aim of this study was to identify novel antigens for CIS and investigate their prognostic potential to predict conversion to multiple sclerosis (MS). We applied serological antigen selection (SAS) to identify antigens interacting with antibodies present in the pooled CSF from four CIS patients, who developed MS. Antibody reactivity towards CIS antigens identified by SAS was tested in CSF and serum from patients with CIS (n = 123/n = 108), MS (n = 65/n =...
NOTELAERS, Kristof; SMISDOM, Nick; Rocha, Susana; JANSSEN, Daniel; Meier, Jochen C.; RIGO, Jean-Michel; Hofkens, Johan; AMELOOT, Marcel
The spatio-temporal membrane behavior of glycine receptors (GlyRs) is known to be of influence on receptor homeostasis and functionality. In this work, an elaborate fluorimetric strategy was applied to study the GlyR alpha 3K and L isoforms. Previously established differential clustering, desensitization and synaptic localization of these isoforms imply that membrane behavior is crucial in determining GlyR alpha 3 physiology. Therefore diffusion and aggregation of homomeric alpha 3 isoform-containing GlyRs were studied in HEK 293 cells. A unique combination of multiple diffraction-limited ensemble average methods and subdiffraction single particle techniques was used in order to achieve an integrated view of...
This book provides up-to-date evidence-based information on why and how to implement exercise intervention in the treatment of obesity. It starts with a description of the epidemiology of obesity, how to execute preparticipation screening in the obese, and the impact of of caloric intake restriction vs exercise training in obese subjects. Next, a detailed description of exercise physiology in obesity is provided, followed by motivation techniques, the impact of training modalities on adipose tissue mass loss, and an exploration of factors related to the heterogeneity of adipose tissue mass loss in the obese when following exercise interventions. In final, the...
Neven, An; Janssens, Davy; Alders, Geert; Wets, Geert; Van Wijmeersch, Bart; Feys, Peter
Background: Persons with Multiple Sclerosis (MS) experience several physical and cognitive problems which can influence their travel behavior. Few data are available about the real participation (restrictions) in daily outdoor activity and travel behaviour. Objective: This pilot study aimed to document, in relation to disease-related disability, which, and how many, activities and trips were daily made by persons with MS, and what transport modes were used. Methods: 36 persons with MS (Expanded Disability Status Scale, EDSS, 1.5-8.0, age 27-63) and 24 healthy controls (age 25-62) were studied, using activity-related travel diaries and GPS tracking devices. Information about overall disability characteristics...
Smets, A.; Nuydens, R.; De Jongh, R.; Pintelon, I.; Thys, S.; Timmermans, J. P.; Rigo, J. M.; Meert, T.
The high levels of histamine in brain after traumatic brain injury and the observed influence of histamine on aquaporin-1 (AQP-1) localization in gastric cells, lead to the hypothesis that histamine could play a major role in the pathophysiology of brain edema An intracerebroventricular (ICV) histamine induced brain edema model was developed in rats. Infusion of concentrations >= 50 mM histamine resulted in a dose-dependent intracranial pressure (ICP) increase and death. Furthermore, histological experiments showed the internalization of membrane-expressed AQP4 after histamine challenge. The decreased fraction of functional membrane-associated AQP4 might result in an increased intracranial p[ressure. In this new experimental...
Heldmann, F.; Brandt, J.; van der Horst-Bruinsma, I. E.; Landewe, R.; Sieper, J.; Burmester, G. R.; van den Bosch, F.; de Vlam, K.; GEUSENS, Piet; Gaston, H.; Schewe, S.; Appelboom, T.; Emery, P.; Dougados, M.; Leirisalo-Repo, M.; Breban, M.; Listing, J.; Braun, J.
Objectives To study the long-term efficacy and safety of treatment with infliximab in patients with ankylosing spondylitis (AS) in a real life setting. Methods AS patients from 6 European countries who had finished the 2-year trial ASSERT were invited to participate in the open-label investigator-driven study EASIC. At baseline, 2 groups were formed: patients of group 1 had not been treated with infliximab after ASSERT, while those of group 2 had continuously received it. Patients of group I were further subdivided in group I a: patients with a relapse and 1b: in remission. All patients of group la and 2...
Bogie, Jeroen F. J.; STINISSEN, Piet; HELLINGS, Niels; HENDRIKS, Jerome
Introduction: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) in which macrophages play a central role. Initially, macrophages where thought to be merely detrimental in MS, however, recent evidence suggests that their functional phenotype is altered following myelin phagocytosis. Macrophages that have phagocytosed myelin may be less inflammatory and may exert beneficial effects. The presence of myelin-containing macrophages in CNS-draining lymph nodes and perivascular spaces of MS patients suggests that these cells are ideally positioned to exert an immune regulatory role. Therefore we evaluated in this study the effect of myelin-phagocytosing macrophages on...
DE JONGH, Rafael; SMETS, Anke; Nuydens, R.; RIGO, Jean-Michel; MEERT, Theo
Inspired by the high histamine levels in the brains of traumatic brain injury (TBI) patients and earlier in vitro results with histamine in a cell swelling model, a histamine induced brain ederna model was developed in rats. In this new experimental model, selective histamine agonists and antagonists were tested. An acute lethal effect is caused by H(1)-antagunism after intracerebroventricular (ICV) histamine infusion. Moreover H(2)-receptor activation results in toxic effects, which are reduced with H1-receptor stimulation. These data indicate that active H(1)-receptors protect against the toxic II,-effect. This shielding effect of H(1)-receptor activity is confirmed in several experiments. Therefore central penetrating...
Hellings, Niels; Janssens, Kris; Hendriks, Jerome; de Vries, H.; Vanwijmeersch, B.; Op't Eijnde, Bert; Van den Haute, C.; Baekelandt, Veerle; Stinissen, Piet; Slaets, H.
Purpose/Objective: The interleukin-6 class cytokines leukemia
inhibitory factor (LIF) and oncostatin M (OSM) are upregulated in
multiple sclerosis (MS) lesions, but their effects on CNS lesion
development are far from understood. LIF and OSM potentially
influence immune responses as well as CNS resident cells during
neuroinflammatory conditions. Importantly, since they activate different
receptors, LIF and OSM can influence these parameters to different
extents. This study was designed to elucidate the role of OSM
and LIF in MS lesion development.
Materials and methods: Stereotactic application of lentiviral vectors
was performed to achieve a stable expression and secretion of LIF or
OSM in the CNS of adult mice. Experimental autoimmune encephalomyelitis
(EAE) was induced...
De Baets, Liesbet; Jaspers, Ellen; Desloovere, Kaat; Van Deun, Sara
Through the onset of post-stroke motor disorders, the normal scapular function is compromised. As a
result, shoulder pain and associated upper limb dysfunctions frequently arise after stroke.
This review aimed to provide a systematic overview of available literature on scapular function, i.e.
scapular three-dimensional (3D) kinematics and muscle activity during elevation, in healthy persons,
persons with primary shoulder disorders and post-stroke patients. 3D scapular kinematics have been
widely reported in healthy persons and persons with primary shoulder disorders, whereby a general pattern
of upward rotation and posterior tilt during elevation has been agreed upon. Results on scapular
internal/external rotation are inconsistent. In a post-stroke population, 3D scapular...
BROUX, Bieke; VAN WIJMEERSCH, Bart; STINISSEN, Piet; HELLINGS, Johan
Purpose/Objective: Immune ageing or immunosenescence, contributes to the increased morbidity and mortality seen in the elderly. Premature immunosenescence is shown to occur in patients with multiple sclerosis(MS). The main characteristic of immunosenescence is the expansion of CD4+ CD28- T cells in the peripheral blood. We showed that these cells accumulate in brain lesions of MS patients CD24+ CD28- T cells have a cytotoxic profile, shown by expression of the cytotoxic molecules perforin, granzyme B and NKG2D, an activating natural killer (NK) cell receptor. For NK cells, it is known that NKG2D expression and cytotoxicity increase in response to interleukin (IL)-15,...
Rosenow, Anja; NOBEN, Jean-Paul; Jocken, Johan; Kallendrusch, Sonja; Fischer-Posovszky, Pamela; Mariman, Edwin C. M.; Renes, Johan
Enlarged white adipose tissue (WAT) is a feature of obesity and leads to changes in its paracrine and endocrine function. Dysfunction of WAT cells is associated with obesity-associated disorders like type 2 diabetes and cardiovascular diseases. Resveratrol (RSV), a natural polyphenolic compound, mimics beneficial effects of calorie restriction. As such, RSV seems a promising therapeutic target for obesity-associated disorders. The effect of RSV on the human adipokine profile is still elusive. Therefore, a proteomic study together with bioinformatical analysis was performed to investigate the effect of RSV on the secretion profile of mature human SGBS adipocytes. RSV incubation resulted in...
Naesens, R.; MAGERMAN, Koen; GYSSENS, Inge; Leenders, A.; Meekelenkamp, J.; Van Esbroeck, M.; Coppens, G.; Oris, E.; Craeghs, J.; Thoelen, I.; Gabriels, P.; Vandevelde, M.; Forier, A. -M.; Waumans, L.; Cartuyvels, R.
Data from three different data sources were compiled to estimate the presence of Coxiella burnetii in the Belgian Limburg province for both humans and livestock. First, serological data of all samples sent to the Belgian reference centre (2003-2010) for human Q fever were analysed, showing evidence for an acute Q fever infection in 1-5% of the cases. Second, a multi-centre prospective survey was conducted in Limburg in 2010 to detect undiagnosed human cases; evidence for a recent infection with Coxiella burnetii was found in three out of 100 patients from which clinicians suspected a Mycoplasma pneumoniae infection. Third, we analyzed...
Verheyen, An; PEERAER, Eve; Nuydens, Rony; Dhondt, Joke; Poesen, Koen; Pintelon, Isabel; Daniels, Anneleen; Timmermans, Jean-Pierre; MEERT, Theo; Carmeliet, Peter; Lambrechts, Diether
Systemic vascular endothelial growth factor inhibition, in combination with chemotherapy, improves the outcome of patients with metastatic cancer. Peripheral sensory neuropathies occurring in patients receiving both drugs are attributed to the chemotherapy. Here, we provide unprecedented evidence that vascular endothelial growth factor receptor inhibitors trigger a painful neuropathy and aggravate paclitaxel-induced neuropathies in mice. By using transgenic mice with altered neuronal vascular endothelial growth factor receptor expression, systemic inhibition of vascular endothelial growth factor receptors was shown to interfere with the endogenous neuroprotective activities of vascular endothelial growth factor on sensory neurons. In vitro, vascular endothelial growth factor prevented primary...
HENDRIX, Sven; NELISSEN, Sofie; LEMMENS, Evi; VANGANSEWINKEL, Tim; VIDAL VERA, Pia; WILLEMS, Leen; Boato,F.; DOOLEY, Dearbhaile; Pejler, G.; Maurer, M.; Metz, Martin
Purpose/Objective: It becomes increasinglyclear that mast cells (MCs) are not only key players in allergic diseases (e.g.asthma), but seem to play a complex role in neuroinflammatory diseases such as multiple sclerosis and stroke. However, their role during and after mechanical CNS trauma is not clear. In the present study, we have investigated the effectsof MC-deficiency on the histological and clinical outcome after spinal cordhemisection at thoraic level T8 resulting
in a complete transection of the dorsomedial and ventral corticospinal tract. Functional recovery in SCI mice was tested with the Basso Mouse Scale. Spinal cord sections were analyzed by immunofluorescence. RTPCR and...
Vanheel, A.; Brone, B.; DANIELS, Ruth; Stinissen, P.; Noben, J. P.; Hellings, N.
Purpose/Objective: A more detailed insight into disease mechanisms of multiple sclerosis (MS) is crucial for the development of new and more effective theories. MS is a chronic inflammatory autoimmune disease of the central nervous system. The aim of this study is to identify novel disease associated proteins that are functionally involved in the MS brain pathology. Materials and methods: In a previous proteomics study, brainstem proteins were obtained from Lewis rats with MBP induced acute experimental autoimmune encephalomyelitis (EAE), a well characterized disease model of MS. Samples were collected at different time points: just before onset of symptoms, at the...